This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The original goal of Area II, Gene Expression and Regulation, was to understand the mechanisms that control gene expression, so that the molecular events that govern cell differentiation and organism development can be elucidated. There are twelve members of Area II whose interests are diverse, but overlap to form clusters of common interest. All but one of these researchers have been hired within the past ten years. Over the years, the research foci of the various areas has undergone much change due to the many recent advances in these fields that have, in turn, spurred faculty recruitment in the departments of physics, biology and chemistry. Because research in gene expression has diverged into several different foci, Area II has become a somewhat large and disorganized subgroup (as stated in our last NIH site visit). We separated the faculty participants into two new Areas. Members of the old Area II subgroup were re- organized into an Immunology Subgroup, comprised of Drs. Guyden, Balogh-Nair, Boto, Coico, Moore together with the more recent hires: Drs. Gottleib, Spatz, and Pezzano (this will become a new area IV). The goal of Area IV, Immunology, is to understand the cell- to-cell interactions and molecular mechanisms that control the development and function of the immune system. Within the group, a smaller subgroup is focused on the mechanisms that regulate autoimmunity, both at the developmental and regulatory levels. There are six members of Area IV, consisting of 2 research active faculty from the CUNY Medical School department of Microbiology and Immunology and 4 from the department of Biology. William Boto, Shubha Govind and Jerry Guyden were hired through the RCMI grant directly. Mark Pezzano was recruited for a faculty position in the Biology department, after serving as Deputy Director of the RCMI program and collaborating on research projects with Dr. Guyden for several years. Paul Gottlieb and Linda Spatz were hired by the CUNY Medical School and recruited to join the RCMI program because of their active research collaboration focused on autoimmunity when the immunology subgroup was initiated in our last proposal. All of these researchers currently have outside funding for their research projects and many have collaborative projects both within the group and with outside investigators. The research interests of the group are diverse, ranging from studies of innate immune system development and function in Drosophila to KSHV transmission and evolution in humans. We have several investigators who study aspects of immune cell development in both B and T cells and immune system regulation, which are focused on a key question in Immunology as to how the immune system distinguishes self from non-self. These studies are directly relevant to the development of autoimmune diseases. The remaining members of the old Area II will become members of a new subgroup with a research focus on the development of cancer and aging (Area II). The rationale for forming a new cancer subgroup within the RCMI is twofold: 1. Disparities in Cancer incidence and treatment is an issue that particularly impacts minority populations. This point is clearly illustrated by the following statistics taken from the NCI website [ HYPERLINK "http://www.nci.nih.gov/newscenter/healthdisparities%5D" http://www.nci.nih.gov/newscenter/healthdisparities] : -African-Americans have an 8.7% greater incidence of cancer overall, and are 29.1% more likely to die from it than caucasians. - African-American women are 21.6% more likely to be diagnosed with colon and rectal cancers and 5.6% more likely to be diagnosed with lung and bronchial cancers than white women. African-American women also have an 86.4% higher incidence of breast cancer than white women and are 32.0% more likely to die from it. -African-American men are 12.9% more likely to be diagnosed with colon and rectal cancers than white men and are 51.6% more likely to be diagnosed with lung and bronchial cancers. Death rates from these cancers are also higher in African-american men - 37.0% and 36.8% greater death rates than white men for these types of cancers, respectively. - African-American men are also 65.6% more likely to be diagnosed with prostate cancer and 141.7% more likely to die from it than their white counterparts. - Hispanic women are 82.8% more likely to be diagnosed with cervical cancer and 37.0% more likely to die from it than caucasian females. Asian/Pacific islanders, American indians/Alaskan natives, Hispanics and African Americans all have a higher incidence of liver cancer (187.5%, 22.9%, 89.6%, 43.8% respectively) and stomach cancer (124.7%, 42.9%, 72.7%, 81.8% respectively) than caucasians. 2. There is already significant scientific expertise, and the nucleus for, a cancer group within area II. Drs. Hubbard and Steinberg currently have ongoing research programs in cancer research and are collaborators on an NIH-funded pilot project with Dr. Irene Orlow at the Memorial Sloan Kettering Cancer Center. In addition, Dr. Hubbard wishes to extend her ongoing research on cell senescence to cancer development as a function of the aging process. As there is a well established direct relationship between cancer incidence and aging (summarized in: Ukraintseva, S. and Yashin, A.: Individual Aging and Cancer Risk: Are They Related? Demographic Research 9:164-195, 2003) it is our desire to hire a new researcher with interests in cancer and aging that will complement their research as well as that of other area II faculty with research in related areas such as cell cycle control and signaling pathways - namely Dr. Govind and the recent hire, Gillian Small. In addition, through the efforts of Dr. Hubbard, department of biology recruited Mary Alpaugh from UCLA. She was asked to join the RCMI program because of her exciting project in tumor biology.